Abstract Hereditary non-syndromic sensorineural hear- ing loss (NSSHL) is a genetically highly heterogeneous group of disorders. Autosomal dominant forms account for up to 20% of cases. To date, 39 loci have been identi- fied by linkage analysis of affected families that segregate NSSHL forms in the autosomal dominant mode (DFNA). Investigation of a large Spanish pedigree with autosomal dominant inheritance of bilateral and progressive NSSHL of postlingual onset excluded linkage to known DFNA loci and, in a subsequent genome-wide scan, the disorder locus was mapped to 3q28–29. A maximum two-point LOD score of 4.36 at θ=0 was obtained for marker D3S1601. Haplotype analysis placed the novel locus, DFNA44, within a 3-cM genetic interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of two genes (CLDN16 and FGF12) in this interval did not reveal dis- ease-causing mutations. Introduction Hearing loss is the most common sensory defect in hu- mans. About 1/1000 children are affected by severe or pro- found sensorineural hearing impairment before speech ac- quisition (prelingual deafness) and genetic causes are esti- mated to be responsible for up to 60% of these cases (Morton 1991; Marazita et al. 1993). On the other hand, postlingual hearing loss is much more frequent, affecting 10% of the population by age 60 and 50% by age 80, re- sulting in the progressive social isolation of the affected individual (Petit 1996; Davis 1989). Most cases of postlin- gual deafness have a multifactorial etiology that results from a combination of genetic and environmental factors but monogenic forms exist that follow a mainly autosomal dominant mode of inheritance, representing about 10– 20% of all cases of hereditary non-syndromic sensorineural hearing loss (NSSHL). Hereditary postlingual hearing loss is usually moderate to severe and progressive and often affects a particular range of frequencies (Bom et al. 1999). So far, more than 70 loci for non syndromic hereditary deaf- ness have been described. Among them, 39 loci (DFNA1- DFNA30, DFNA32-DFNA38, DFNA40 and DFNA41) have been identified in familial cases with autosomal dominant sensorineural hearing loss (ADNSSHL) and 17 genes have been cloned (Van Camp and Smith 2002). In this study, we have identified a novel DFNA locus on chromosome 3q28–29 in a Spanish family with postlin- gual and progressive hearing loss. Materials and methods Nomenclature Gene symbols used in this article follow the recommendations of the HUGO Gene Nomenclature Committee (Povey et al. 2001). Family data A five-generation family (S281) with a history of ADNSSHL was ascertained through the Hospital Universitario “Puerta del Mar”, Cádiz, in southern Spain. It consists of 40 members, 18 of whom are affected (Fig. 1). Appropriate informed consent was obtained from all study participants. Clinical evaluation was performed and blood samples were collected from 27 family members. DNA was extracted by standard techniques. Environmental factors were ex- Silvia Modamio-Høybjør · Miguel Angel Moreno-Pelayo · Angeles Mencía · Ignacio del Castillo · Sebastian Chardenoux · Daniel Armenta · Mark Lathrop · Christine Petit · Felipe Moreno A novel locus for autosomal dominant nonsyndromic hearing loss (DFNA44) maps to chromosome 3q28–29 Hum Genet (2003) 112 : 24–28 DOI 10.1007/s00439-002-0836-x Received: 16 July 2002 / Accepted: 20 August 2002 / Published online: 16 October 2002 ORIGINAL INVESTIGATION S. Modamio-Høybjør and M. A. Moreno-Pelayo contributed equally to this work and the order of authorship is arbitrary S. Modamio-Høybjør · M.A. Moreno-Pelayo · A. Mencía · I. del Castillo · F. Moreno (✉) Unidad de Genética Molecular, Hospital Ramón y Cajal, Carretera de Colmenar Km 9, 28034, Madrid, Spain e-mail: fmoreno@hrc.insalud.es, Tel.: +34-91-3368541, Fax: +34-91-3369016 S. Chardenoux · C. Petit Unité de Genetique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, Paris, France D. Armenta Unidad de Genética, Hospital Universitario “Puerta del Mar”, Cadiz, Spain M. Lathrop Centre National de Genotypage, Evry, France © Springer-Verlag 2002